1. Field of the Invention
The present invention relates generally to methods for the treatment of cancer. More specifically, the invention relates to methods of treating cancers, such as, acute myeloid leukemia using a combination therapy.
2. Description of the Related Art
Few therapeutic options exist for patients with relapsed or refractory acute myeloid leukemia (AML). A similar dilemma exists for patients with acute myeloid leukemia whose age or comorbid conditions preclude traditional cytarabine- and anthracycline-based regimens. Decitabine and azacitidine are DNA methyltransferase inhibitors that have been adopted as an alternative to high-dose induction chemotherapy for acute myeloid leukemia patients who cannot tolerate or whose disease has failed aggressive induction.
Acute myeloid leukemia is genetically very heterogeneous which has contributed to many failed attempts for targeting any particular mutation (1). Cellular oxidative state is a credible alternative target to selectively eradicate acute myeloid leukemia cells because it is a fundamental property of each cell that is sufficiently different between leukemic and normal cells, yet its aberrancy is shared among different acute myeloid leukemia cells.
Dichloroacetate binds to the active site of pyruvate dehydrogenase kinase and inactivates its kinase activity thus shunting more pyruvate into mitochondria and away from conversion to lactate. Arsenic trioxide is approved for treatment of patients with acute promyelocytic leukemia (APL) whose disease failed to respond to or relapsed following all-trans retinoic acid/anthracycline therapy. In acute promyelocytic leukemia, arsenic trioxide induces both differentiation and apoptosis of leukemic cells (2). High concentrations of arsenic trioxide appear to be a limiting factor for clinical use due to severe treatment-related adverse events.
Thus, the prior art is deficient in methods to treat cancers such as acute myeloid leukemia using a synergistic combination drug treatment. The present invention fulfills this longstanding need and desire in the art.